OBJECTIVES:

Regulatory authorities (RA) have issued guidances regarding the need for long-term follow-up (LTFU) of patients treated with cell and gene therapy (CGT) to monitor durability of effect as well as safety, over periods up to 15 years. LTFU are also useful for Health Technology Assessment (HTA) evaluations. This however, poses technical and operational challenges.

METHODS:

We have identified two main sets of challenges for LTFU of patients treated with CGT and have analysed their potential consequences and possible mitigation strategies.

RESULTS:

Patient retention: over 15 years, pediatric patients become adults, can change geography and medical setting. A LTFU study must be able to follow patients throughout their life changes without burdening them. One mitigation strategy is the application of a decentralized patient-centric virtual model where the point of contact is the patient and not the site and where data collection is supported by an external central site model.

Post-marketing LTFU: LTFU are also required for patients receiving the therapy after marketing authorization (MA). Beyond the application of relevant safety reporting rules, LTFU warrant tailored recruitment strategies for efficient enrolment. A mitigation is to consider LTFU as product registries and to start designing them before MA, e.g. by liaising with RA, HTAs, disease registries and/or sites susceptible to dispense the therapy, and patient advocacy groups, to organize an early study framework, as recommended by current registry guidances.

An additional consideration is the need for consistency in the data collection between the LTFU of patients exposed in clinical trials and the LTFU of patients exposed in the post-marketing period, to allow pooling of the data in the frequent context of low sample size.

CONCLUSIONS:

LTFU of patients receiving CGT raise specific issues that can be mitigated by latest developments in registry research, via early collaboration and via a virtualization of operations.